33 research outputs found
Anti-tumor activity mediated by protein and peptide transduction of HIV viral protein R (Vpr)
Peptides that are capable of traversing the cell membrane, via protein transduction domains (PTDs), are attractive either directly as drugs or indirectly as carriers for the delivery of therapeutic molecules. One such PTD, a HIV-1 Tat derived peptide has successfully delivered a variety of "cargoes" including proteins, peptides and nucleic acids into cells. There also exists other naturally occurring membrane permeable peptides which have potential as PTDs. Specifically, one of the accessory proteins of HIV (viral protein R; i.e., Vpr), which is important in controlling viral pathogenesis, possesses cell transduction domain characteristics. Related to these characteristics, Vpr has also been demonstrated to induce cell cycle arrest and host/target cell apoptosis, suggesting a potential anticancer activity for this protein. In this report we assessed the ability of Vpr protein or peptides, with or without conjugation to a PTD, to mediate anti-cancer activity against several tumor cell lines. Specifically, several Vpr peptides spanning carboxy amino acids 65-83 induced significant (i.e., greater than 50%) in vitro growth inhibition/toxicity of murine B16.F10 melanoma cells. Likewise, in in vitro experiments with other tumor cell lines, conjugation of Vpr to the Tat derived PTD and transfection of this construct into cells enhanced the induction of in vitro apoptosis by this protein when compared to the effects of transfection of cells with unconjugated Vpr. These results underscore the potential for Vpr based reagents as well as PTDs to enhance anti-tumor activity, and warrants further examination of Vpr protein and derived peptides as potential therapeutic agents against progressive cell proliferative diseases such as cancer. ©2009 Landes Bioscience
Current status of groundnut improvement in Uganda
In Uganda, groundnut (Arachis hypogaea L) is the second most
important legume after beans. Groundnuts is cultivated on
nearly 260,000 ha, representing 24.6% of the total arable
land. On-farm pod yields are low, averaging 800 kg/ha of dry
pods, compared to on-station potential yields of 3,000kg/ha.
Sales from current production could potentially generate $344
million to the producers who are largely small-scale farmers.
The yield gaps are attributed to a combination of biotic, abiotic,
cultural and political factors. Since the 1920s, research efforts
have released 24 varieties, the most recent commercial varieties
being the Serenut 1-14 series. These varieties have overcome
some of the mentioned production constraints. However,
varied growing agroecologies, land tenure systems, diverse
market preferences, and emerging stresses call for continuous
research. Current research agenda includes breeding for high
oleic, leafminer resistance, confectionery, aflatoxin tolerance,
drought tolerance, early to medium maturing varieties, high
yielding, and rosette disease resistant varieties. We have initiated
Marker Assisted Selection for high oleic breeding and
adopted BMS for Digitalization of data capture, management,
analyses and storage. Recently developed regeneration protocol
will aid in introgressing additional traits across taxa. The
bimodal rainfall pattern and active hybridization programme
increases our breeding cycles. To date, the groundnut breeding
program has an active breeding pipeline frequently releasing
varieties and lines which have already been shared with National
Programs across Africa, Haiti and the USA with many
additional National Programs making requests. We have strong
partnerships in Research and Development among the African
Countries, USAID, ICRISAT, and BMGF
Electroporation-Mediated Delivery of a Naked DNA Plasmid Expressing VEGF to the Porcine Heart Enhances Protein Expression
Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly increased cardiac expression of VEGF compared with injection of plasmid alone. This is the first report showing successful intracardiac delivery, through in vivo EP, of a protein expressing plasmid in a large animal
Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu(+ )metastatic breast cancer in mice
INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu(+ )cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified